For the last several years, our work in human aging has focused primarily on the influence of chronic exercise on cardiovascular function and autonomic nervous system circulatory control. In the proposed studies, we shift our focus to sympathetic nervous system (SNS) regulation during acute exercise and other forms of "stress." There is a widely held view that with advancing age efferent SNS activity becomes elevated at rest and that the magnitude of the SNS response to acute stress is increased. However, the experimental basis for this concept is rather weak, the data being primarily derived from peripheral venous measurements of plasma norepinephrine (NE), an imprecise and potentially misleading index of SNS activity. The purpose of the present studies will be to rigorously test the hypothesis that a "hypersympathetic state" develops with human aging. To do so, we will employ a unique and comprehensive experimental approach. Efferent SNS activity will either be directly measured using microneurography or will be estimated from measurements of NE spillover into plasma. Regional SNS diversity will be assessed using microneurographic measurements of sympathetic nerve activity to skeletal muscle (MSNA) and skin (SSNA), and by determining plasma NE spillover to the heart and kidney; concurrent measurements of total (whole-body) plasma NE spillover will provide insight into SNS activity in regions not directly studied. Since age-related changes in SNS behavior may be "condition- specific", SNS activity will be determined both at rest and in response to different types of acute stress including isometric handgrip and dynamic leg cycling (exercise stress), orthostasis (postural stress), local cold (thermal stress), hypoxemia (environmental stress), and cognitive challenge (mental stress); most of these "stressors" will be applied at several levels since aging differences may be stimulus-dependent. To minimize intragroup variability while optimizing the potential for identifying possible age-associated differences, SNS activity will be compared in groups of subjects aged 29-30 yr versus 65-75 yr. Furthermore, because age-related changes in SNS behavior could be gender-specific, subgroups of men and women will be studied in each age range. Finally, since chronic cardiovascular disease, obesity, and decreased physical activity levels could influence SNS activity independent of aging, the young and older subjects will be thoroughly evaluated to ensure that these factors do not confound the interpretation of the results. In addition to the physiological question posed, these studies should have important clinical relevance since: 1) elevated SNS activity at rest and exaggerated SNS reactivity to acute stress are thought to be linked to the development of hypertension, heart and kidney disease, and 2) the prevalence of these pathological conditions increases with aging. Thus, information gained from the proposed studies would provide the experimental evidence to either support or refute an SNS etiology for these and other age-related disorders.